Era of Hope 2011 Investigator Vignette

Title: Inhibition of IGF-1 for Breast Cancer Prevention and Treatment

Investigator: David L. Kleinberg, MD; New York University School of Medicine and Veterans Affairs Medical Center, New York, NY

The focus of our research is to look at the importance of a hormone IGF-1 that underlies the importance of other hormones and other functions in the mammary gland. We believe that by inhibiting this hormone, IGF-1, that we will have wider application to breast cancer prevention and also breast cancer treatment, and it will give us a chance to look at more advanced breast cancers than just the early breast cancers.

Our laboratory has been engaged in looking at the hormonal effects of normal mammary development. We know that estrogen is very important in mammary development but estrogen cannot work unless there’s another hormone called IGF-1 that’s present. Our work has shown that a drug that inhibits IGF-1 action fully inhibits estrogen action; it also inhibits progesterone action, and it also has other actions in the—in the mammary gland that are independent of hormones, so it is possible that there can be several areas where IGF-1 inhibition can be effective. And IGF-1 inhibition by SOM 230 works directly on the mammary gland.

Based on these findings in animals and rats and mice, the DoD awarded us a Synergistic Idea Grant to determine whether the same thing that happens in rats and mice would happen in humans with breast disease. We gave 15 women 10 days of treatment with SOM230 and at the end of that 10-day period, their other lesions were removed; and the lesions from the initial core biopsy were compared to the excision biopsy. We found that there was a significant inhibition of cell proliferation which means that the number pre-malignant cells was—was reduced, and there was also an increase in cell death due to this medication in a period of 10 days.

Now the medication is not without side effects. There is a moderate elevation in glucose when you start giving the medication. And this is due to a reduction in insulin. Other people have looked at—at this—this abnormality, and when they have given the drug for longer periods than 10 days, they’ve noted that this side effect goes away.

Generally, the drug is well tolerated although we haven't tested it in patients with overt diabetes. During this Synergistic Idea Grant—we inadvertently included a patient who had a pre-malignant lesion but also had an area of ductal carcinoma in situ in her mammary gland and this had been missed on the core biopsy. So she was inadvertently included in this, but the result was positive,

If you look at this histology on the left side, this is before treatment and on the right side, this is after treatment. Here there is a 3.4% index of cell proliferation before treatment and that was reduced 0.9% after treatment. There was also a small increase in cell death; it was 0.1% before treatment and 0.4% after treatment. This plus our previous findings led to the DoD awarding us an Expansion Grant which we’re doing now. We’ve just started to enlist volunteers with DCIS to join our study.

And instead of 10 days, we plan to treat them for 20 days for several reasons. One being we want to see if the glucose side effect goes away, and the other being that we want to look at what happens to the tumor with a very special kind of MRI analysis before and after treatment. We hope that we will find that most of the DCIS(es) will respond the way this one patient did.

We’re thrilled that our partnership with the DoD has permitted us to look at these new possibilities in treating breast cancer, and we hope that they will have positive effects on treatments in the future.